Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients

{ 'indexed': { 'date-parts': [[2023, 10, 20]], 'date-time': '2023-10-20T05:35:50Z', 'timestamp': 1697780150409}, 'reference-count': 24, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2023, 10, 19]], 'date-time': '2023-10-19T00:00:00Z', 'timestamp': 1697673600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>In 2019, a highly pathogenic coronavirus ' 'named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in ' 'the outbreak of coronavirus disease 2019 (COVID-19). With the aim of finding effective drugs ' 'to fight against the disease, several trials have been conducted since COVID-19 can only be ' 'considered a treatable disease, from a clinical point of view, after the availability of ' 'specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a ' 'potential treatment for COVID-19 as it has the capability to lower the patient’s viral load ' 'and promote ' 'recovery.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Volunteers ' 'infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction ' '(RT-PCR), with good kidney and liver function, who were not using other antivirals or ' 'monoclonal antibodies were eligible. Samples from patients were assessed for viral load every ' '48\u2009h during treatment using reverse transcription quantitative polymerase chain reaction ' '(RT-qPCR) and droplet digital polymerase chain reaction ' '(ddPCR).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The study’s ' 'primary outcome measure was the percentage of participants showing an improvement in clinical ' 'scores, while the secondary outcome measure was the percentage of participants with a ' 'clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC ' 'for treating COVID-19. In the analysis of sociodemographic variables, no significant ' 'differences were detected between patients in the FNC and the placebo group for race, age ' 'group, or sex. The results showed a potential benefit to participants who received FNC during ' 'the study, as observed in the shorter hospital stay, shorter negative conversion time of ' 'SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever ' 'and chills were significant at D1, D2, and D3. In this study, a total of 112 adverse events ' 'cases were noted, with 105 cases being categorized as non-serious and only 7 cases as serious ' 'adverse events.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The ' 'pandemic is not being effectively controlled and is causing multiple waves of infection that ' 'require extensive medical resources. However, FNC has demonstrated potential to reduce the ' 'treatment duration of moderate COVID-19 cases, thereby saving significant medical resources. ' 'This makes FNC a promising candidate for COVID-19 ' 'treatment.</jats:p><jats:p><jats:bold>Clinical trial registration</jats:bold>: ' '[<jats:ext-link>clinicaltrials.gov</jats:ext-link>], identifier ' '[NCT04668235].</jats:p></jats:sec>', 'DOI': '10.3389/fmed.2023.1215916', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 10, 19]], 'date-time': '2023-10-19T07:09:43Z', 'timestamp': 1697699383000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety ' 'and clinical efficacy of AZVUDINE in moderate COVID-19 patients', 'prefix': '10.3389', 'volume': '10', 'author': [ {'given': 'Sávio Bastos', 'family': 'de Souza', 'sequence': 'first', 'affiliation': []}, {'given': 'Paula Gebe Abreu', 'family': 'Cabral', 'sequence': 'additional', 'affiliation': []}, {'given': 'Renato Martins', 'family': 'da Silva', 'sequence': 'additional', 'affiliation': []}, {'given': 'Raul Ferraz', 'family': 'Arruda', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Sheila Passos de Figueiredo', 'family': 'Cabral', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Arícia Leone Evangelista Monteiro', 'family': 'de Assis', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Antônio Brazil', 'family': 'Viana Junior', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Wim Maurits Sylvain', 'family': 'Degrave', 'sequence': 'additional', 'affiliation': []}, {'given': 'Aline dos Santos', 'family': 'Moreira', 'sequence': 'additional', 'affiliation': []}, {'given': 'Cléber Glória', 'family': 'Silva', 'sequence': 'additional', 'affiliation': []}, {'given': 'Junbiao', 'family': 'Chang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pingsheng', 'family': 'Lei', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2023, 10, 19]]}, 'reference': [ { 'key': 'ref1', 'doi-asserted-by': 'publisher', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'article-title': 'A novel coronavirus from patients with pneumonia in China, 2019', 'volume': '382', 'author': 'Zhu', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': 'ref2', 'doi-asserted-by': 'publisher', 'first-page': '706', 'DOI': '10.1093/cid/ciaa199', 'article-title': 'Clinical characteristics of imported cases of COVID- 19 in Jiangsu ' 'Province: a multicenter descriptive study', 'volume': '71', 'author': 'Wu', 'year': '2020', 'journal-title': 'Clin Infect Dis'}, { 'key': 'ref3', 'doi-asserted-by': 'publisher', 'first-page': '538', 'DOI': '10.1002/jmv.25721', 'article-title': 'Combination of RT-qPCR testing and clinical features for diagnosis of ' 'COVID-19 facilitates management of SARS-CoV-2 outbreak', 'volume': '92', 'author': 'Wang', 'year': '2020', 'journal-title': 'J Med Virol'}, { 'key': 'ref4', 'doi-asserted-by': 'publisher', 'first-page': '999', 'DOI': '10.1016/j.scib.2022.02.011', 'article-title': 'COVID-19 can be called a treatable disease only after we have ' 'antivirals', 'volume': '67', 'author': 'Zhang', 'year': '2022', 'journal-title': 'Sci. Bull'}, { 'key': 'ref5', 'doi-asserted-by': 'publisher', 'first-page': '1813', 'DOI': '10.1056/NEJMoa2007764', 'article-title': 'Remdesivir for the treatment of Covid-19—final report', 'volume': '383', 'author': 'Beigel', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'key': 'ref6', 'doi-asserted-by': 'publisher', 'first-page': '1384', 'DOI': '10.1681/ASN.2020050589', 'article-title': 'Remdesivir in patients with acute or chronic kidney disease and ' 'COVID-19', 'volume': '31', 'author': 'Adamsick', 'year': '2020', 'journal-title': 'J Am Soc Nephrol'}, { 'key': 'ref7', 'doi-asserted-by': 'publisher', 'first-page': '2020', 'DOI': '10.1101/2020.12.10.419242', 'article-title': 'The combined treatment of Molnupiravir and Favipiravir results in a ' 'marked potentiation of efficacy in a SARS-CoV2 hamster infection model ' 'through an in- creased frequency of mutations in the viral genome', 'author': 'Abdelnabi', 'year': '2021', 'journal-title': 'bioRxiv'}, { 'key': 'ref8', 'doi-asserted-by': 'publisher', 'first-page': '447', 'DOI': '10.1038/nrd4010', 'article-title': 'Advances in the development of nucleoside and nucleotide analogues for ' 'cancer and viral diseases', 'volume': '12', 'author': 'Jordheim', 'year': '2013', 'journal-title': 'Nat Rev Drug Discov'}, { 'key': 'ref9', 'doi-asserted-by': 'publisher', 'first-page': 'e2001435', 'DOI': '10.1002/advs.202001435', 'article-title': 'A randomized, open-label, controlled clinical trial of AZVUDINE tablets ' 'in the treatment of mild and common COVID-19, a pilot study', 'volume': '7', 'author': 'Ren', 'year': '2020', 'journal-title': 'Adv Sci'}, { 'key': 'ref10', 'doi-asserted-by': 'publisher', 'first-page': '656', 'DOI': '10.1016/S1473-3099(20)30232-2', 'article-title': 'Viral dynamics in mild and severe cases of COVID-19', 'volume': '20', 'author': 'Liu', 'year': '2020', 'journal-title': 'Lancet Infect Dis'}, { 'key': 'ref11', 'doi-asserted-by': 'publisher', 'first-page': 'e4197', 'DOI': '10.1093/cid/ciaa851', 'article-title': 'Impact of SARS-CoV-2 viral load on risk of intubation and mortality ' 'among hospitalized patients with coronavirus disease 2019', 'volume': '73', 'author': 'Magleby', 'year': '2020', 'journal-title': 'Clin Infect Dis'}, { 'key': 'ref12', 'doi-asserted-by': 'publisher', 'first-page': '5493', 'DOI': '10.1038/s41467-020-19057-5', 'article-title': 'SARS-CoV-2 viral load is associated with increased disease severity and ' 'mortality', 'volume': '11', 'author': 'Fajnzylber', 'year': '2020', 'journal-title': 'Nat Commun'}, { 'key': 'ref13', 'doi-asserted-by': 'publisher', 'first-page': 'E70', 'DOI': '10.1016/S2213-2600(20)30354-4', 'article-title': 'SARS-CoV-2 viral load predicts COVID-19 mortality', 'volume': '8', 'author': 'Pujadas', 'year': '2020', 'journal-title': 'Lancet Respir Med'}, { 'key': 'ref14', 'volume-title': 'Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected ' 'human cases', 'year': ''}, { 'key': 'ref15', 'doi-asserted-by': 'publisher', 'first-page': '1951', 'DOI': '10.1002/jmv.21026', 'article-title': 'Respiratory syncytial virus infections in hospitalized infants: ' 'association between viral load, virus subgroup, and disease severity', 'volume': '79', 'author': 'Fodha', 'year': '2007', 'journal-title': 'J Med Virol'}, { 'key': 'ref16', 'doi-asserted-by': 'publisher', 'first-page': '369m1443', 'DOI': '10.1136/bmj.m1443', 'article-title': 'Viral load dynamics and disease severity in patients infected with ' 'SARS-CoV-2 in Zhejiang province, China, January–march 2020: ' 'retrospective cohort study', 'volume': '2020', 'author': 'Zheng', 'year': '2020', 'journal-title': 'BMJ'}, { 'key': 'ref17', 'doi-asserted-by': 'publisher', 'first-page': '411', 'DOI': '10.1016/S1473-3099(20)30113-4', 'article-title': 'Viral load of SARS-CoV-2 in clinical samples', 'volume': '20', 'author': 'Pan', 'year': '2020', 'journal-title': 'Lancet Infect Dis'}, { 'key': 'ref18', 'doi-asserted-by': 'publisher', 'first-page': '793', 'DOI': '10.1093/cid/ciaa345', 'article-title': 'Quantitative detection and viral load analysis of SARS-CoV-2 in ' 'infected patients', 'volume': '71', 'author': 'Yu', 'year': '2020', 'journal-title': 'Clin Infect Dis'}, { 'key': 'ref19', 'doi-asserted-by': 'publisher', 'first-page': '1143485', 'DOI': '10.3389/fmed.2023.1143485', 'article-title': 'Serial viral load analysis by DDPCR to evaluate FNC efficacy and safety ' 'in the treatment of mild cases of COVID-19', 'volume': '10', 'author': 'da Silva', 'year': '2023', 'journal-title': 'Front Med'}, { 'key': 'ref20', 'doi-asserted-by': 'publisher', 'first-page': 'e00297-20', 'DOI': '10.1128/JCM.00297-20', 'article-title': 'Negative nasopharyngeal and oropharyngeal swab does not rule out ' 'COVID-19', 'volume': '58', 'author': 'Winichakoon', 'year': '2020', 'journal-title': 'J Clin Microbiol'}, { 'key': 'ref21', 'doi-asserted-by': 'publisher', 'first-page': 'e02290', 'DOI': '10.1128/aac.02290-20', 'article-title': 'A valid warning or clinical Lore: an evaluation of safety outcomes of ' 'Remdesivir in patients with impaired renal function from a multicenter ' 'matched cohort', 'volume': '65', 'author': 'Ackley', 'year': '2020', 'journal-title': 'Antimicrob Agents Chemother'}, { 'key': 'ref22', 'doi-asserted-by': 'publisher', 'first-page': '290', 'DOI': '10.1373/clinchem.2014.230227', 'article-title': 'Next generation digital PCR measurement of hepatitis B virus copy ' 'number in formalin-fixed paraffin-embedded hepatocellular carcinoma ' 'tissue', 'volume': '61', 'author': 'Huang', 'year': '2015', 'journal-title': 'Clin Chem'}, { 'key': 'ref23', 'doi-asserted-by': 'publisher', 'first-page': '244', 'DOI': '10.1038/s41586-019-1027-4', 'article-title': 'HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell ' 'transplantation', 'volume': '568', 'author': 'Gupta', 'year': '2019', 'journal-title': 'Nature'}, { 'key': 'ref24', 'doi-asserted-by': 'publisher', 'first-page': '878', 'DOI': '10.1016/j.jiph.2022.07.002', 'article-title': 'A comprehensive genomic study, mutation screening, phylogenetic and ' 'statistical analysis of SARS-CoV-2 and its variant omicron among ' 'different countries', 'volume': '15', 'author': 'Ahmad', 'year': '2022', 'journal-title': 'J Infect Public Health'}], 'container-title': 'Frontiers in Medicine', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2023.1215916/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 10, 19]], 'date-time': '2023-10-19T07:09:49Z', 'timestamp': 1697699389000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fmed.2023.1215916/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 10, 19]]}, 'references-count': 24, 'alternative-id': ['10.3389/fmed.2023.1215916'], 'URL': 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